<<< Full experiment listing

PXD039474-1

PXD039474 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDual IKZF2 and CK1α degrader targets acute myeloid leukemia cells
DescriptionAcute myeloid leukemia (AML) is a hematologic malignancy for which several epigenetic regulators have been identified as therapeutic targets. Here we report the development of cereblon-dependent degraders of IKZF2 and casein kinase 1 alpha (CK1α) termed DEG-35 and DEG-77. We utilized a structure-guided approach to develop DEG-35 as a nanomolar degrader of IKZF2, a hematopoietic specific transcription factor that contributes to myeloid leukemogenesis. DEG-35 possesses additional substrate specificity for the therapeutically relevant target CK1α which was identified through unbiased proteomics and a PRISM screen assay. Degradation of IKZF2 and CK1α blocks cell growth and induces myeloid differentiation in AML cell lines through CK1α–p53- and IKZF2-dependent pathways. Target degradation by DEG-35 or the analog DEG-77 delays leukemia progression in murine and human AML mice models. Overall, we provide a strategy for multi-targeted degradation of IKZF2/CK1α to enhance efficacy against AML that may be expanded to additional targets and indications.
HostingRepositoryPRIDE
AnnounceDate2023-03-08
AnnouncementXMLSubmission_2023-03-08_09:00:34.937.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterDavidMiyamoto
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-01-16 08:18:31ID requested
12023-03-08 09:00:35announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: targeted protein degradation
acute myeloid leukemia
casein kinase 1 alpha
IKZF2
Contact List
ChristinaWoo
contact affiliationHarvard University
contact emailcwoo@chemistry.harvard.edu
lab head
DavidMiyamoto
contact affiliationHarvard University
contact emaildavidmiyamoto@g.harvard.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/03/PXD039474
PRIDE project URI
Repository Record List
[ + ]